Residual moisture content in low temperature hot melt extrusion and FFF 3D printing of personalized immediate release spironolactone printlets

Abstract

Three-dimensional (3D) printing is increasingly recognized as a promising manufacturing strategy for personalized pediatric medicines. However, robust manufacturing of pharmaceutical filaments remains challenging. This study investigated the feasibility of combining low temperature hot melt extrusion (HME) and fused filament fabrication (FFF) 3D printing to produce immediate-release spironolactone dosage forms with particular emphasis on the influence of wet granulation and residual moisture content on processability and product quality.

Spironolactone was incorporated into Eudragit® EPO-based formulations and processed into drug-loaded filaments. Wet granulation improved powder homogeneity and feeding stability while residual moisture was identified as a critical process parameter affecting extrusion behaviour, filament formation, dimensional consistency and drug distribution. Optimal moisture levels enabled stable low temperature extrusion and reproducible filament production.

Thermal and solid-state characterization confirmed drug stability during processing and revealed a reduction in spironolactone crystallinity indicating enhanced molecular dispersion within the polymer matrix. The resulting filaments exhibited suitable rheological and mechanical properties for FFF printing enabling the fabrication of printlets with different dose strengths and geometries. Printed dosage forms showed rapid disintegration under acidic conditions and immediate-release dissolution profiles. Preliminary pilot-scale runs demonstrated good process reproducibility.

These findings highlight moisture control as a key factor for reliable HME-FFF manufacturing of personalized immediate-release spironolactone printlets.

Continue reading here

Materials

Eudragit®E PO was provided by Evonik Industries (Germany). Kollisolv®1450 was kindly offered by BASF Pharma (Germany). Croscarmellose sodium (CCS) was purchased from Shaanxi Haibo Biotechnology Co., Ltd (Hong Kong, China). Spironolactone (SPR, purity ≥99%) was generously supplied by Armand Trousseau Pediatric Hospital (APHP, Paris, France) and by Delpharm (France). Acetonitrile (HPLC grade) was provided by Merck (Germany). Ultrapure water was made using a Milli-Q® system (Millipore, USA).

Veronica Ianno, Maxime Dorchies, Xavier Séjean, Christophe Bourdette, Luc Ordynski, Philippe Espeau, Residual moisture content in low temperature hot melt extrusion and FFF 3D printing of personalized immediate release spironolactone printlets, Journal of Drug Delivery Science and Technology, Volume 127, Part 3, 2027, 109057, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2026.109057.